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J Neurosurg. 2019 Feb 8:1-7. doi: 10.3171/2018.10.JNS181659. [Epub ahead of print]

Human caudate nucleus subdivisions in tinnitus modulation.

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Departments of1Otolaryngology-Head and Neck Surgery and.
3Surgical Services, San Francisco Veterans Affairs Medical Center; and.
Departments of4Radiology and Biomedical Imaging and.
5Neurological Surgery, University of California, San Francisco, California.


OBJECTIVEThe object of this study was to define caudate nucleus locations responsive to intraoperative direct electrical stimulation for tinnitus loudness modulation and relate those locations to functional connectivity maps between caudate nucleus subdivisions and auditory cortex.METHODSSix awake study participants who underwent bilateral deep brain stimulation (DBS) electrode placement in the caudate nucleus as part of a phase I clinical trial were analyzed for tinnitus modulation in response to acute stimulation at 20 locations. Resting-state 3-T functional MRI (fMRI) was used to compare connectivity strength between centroids of tinnitus loudness-reducing or loudness-nonreducing caudate locations and the auditory cortex in the 6 DBS phase I trial participants and 14 other neuroimaging participants with a Tinnitus Functional Index > 50.RESULTSAcute tinnitus loudness reduction was observed at 5 caudate locations, 4 positioned at the body and 1 at the head of the caudate nucleus in normalized Montreal Neurological Institute space. The remaining 15 electrical stimulation interrogations of the caudate head failed to reduce tinnitus loudness. Compared to the caudate head, the body subdivision had stronger functional connectivity to the auditory cortex on fMRI (p < 0.05).CONCLUSIONSAcute tinnitus loudness reduction was more readily achieved by electrical stimulation of the caudate nucleus body. Compared to the caudate head, the caudate body has stronger functional connectivity to the auditory cortex. These first-in-human findings provide insight into the functional anatomy of caudate nucleus subdivisions and may inform future target selection in a basal ganglia-centric neuromodulation approach to treat medically refractory tinnitus.Clinical trial registration no.: NCT01988688 (


DBS = deep brain stimulation; EPI = echo-planar imaging; LC = locus of caudate; MER = microelectrode recording; MNI = Montreal Neurological Institute; TFI = Tinnitus Functional Index; caudate nucleus; deep brain stimulation; fMRI; fMRI = functional MRI; functional neurosurgery; resting-state functional connectivity; tinnitus

[Available on 2020-08-08]

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